Department of Chemistry of Drugs, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
Department of Pharmacodynamics, Faculty of Pharmacy, Medical College, Jagiellonian University, Medyczna 9, 30-688 Krakow, Poland.
Bioorg Med Chem. 2019 Apr 15;27(8):1619-1628. doi: 10.1016/j.bmc.2019.03.007. Epub 2019 Mar 2.
Gastrotoxicity continues to be a major issue in therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). Medicine is yet to develop absolutely safe analgesics. Numerous strategies are employed to discover new, safer NSAIDs, for example selective inhibition of cyclooxygenase-2, new molecular targets (e.g. microsomal prostaglandin E synthase-1), incorporation of cytoprotective compounds in the drug molecule or modification of the classic NSAIDs currently available on the market. The research presented in this paper is indicative of a current worldwide trend in this area of science, and is an example of the fourth strategy noted above. Two series of new arylpiperazine derivatives of the classic NSAID - piroxicam, were developed by conventional synthesis. The full range of compounds obtained proved to be between two and five times analgesically more potent than the reference drug and, most importantly, they did not show any ulcerogenic activity.
胃肠道毒性仍然是非甾体抗炎药（NSAIDs）治疗中的一个主要问题。医学尚未开发出绝对安全的镇痛药。人们采用了许多策略来发现新的、更安全的 NSAIDs，例如选择性抑制环氧化酶-2、新的分子靶点（例如微粒体前列腺素 E 合酶-1）、在药物分子中加入细胞保护化合物或修饰目前市场上的经典 NSAIDs。本文介绍的研究反映了这一科学领域当前的全球趋势，是上述第四个策略的一个例子。通过常规合成，开发了两种新型经典 NSAID - 吡罗昔康的芳基哌嗪衍生物系列。所得的全系列化合物被证明在镇痛方面比参考药物强 2 到 5 倍，最重要的是，它们没有表现出任何致溃疡活性。
